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Ref Type Journal Article
PMID (28963140)
Authors Zboralski D, Hoehlig K, Eulberg D, Frömming A, Vater A
Title Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade.
Journal Vol Issue Date Pages Journal Short Title
Cancer immunology research 5 11 2017 11 950-956 Cancer Immunol Res
URL
Abstract Text Immune checkpoint inhibitors promote T cell-mediated killing of cancer cells; however, only a subset of patients benefit from the treatment. A possible reason for this limitation may be that the tumor microenvironment (TME) is immune privileged, which may exclude cytotoxic T cells from the vicinity of cancer cells. The chemokine CXCL12 is key to the TME-driven immune suppression. In this study, we investigated the potential of CXCL12 inhibition by use of the clinical-stage l-RNA-aptamer NOX-A12 (olaptesed pegol) to increase the number of tumor-infiltrating lymphocytes. We used heterotypic tumor-stroma spheroids that mimic a solid tumor with a CXCL12-abundant TME. NOX-A12 enhanced the infiltration of T and NK cells in a dose-dependent manner. NOX-A12 and PD-1 checkpoint inhibition synergistically activated T cells in the spheroids, indicating that the agents complement each other. The findings were validated in vivo in a syngeneic murine model of colorectal cancer in which the addition of NOX-A12 improved anti-PD-1 therapy. Taken together, our work shows that CXCL12 inhibition can break the immune-privileged status of the TME by paving the way for immune effector cells to enter into the tumor, thereby broadening the applicability of checkpoint inhibitors in cancer patients. Cancer Immunol Res; 5(11); 950-6. ©2017 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
NOX-A12 NOX-A12 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
NOX-A12 Olaptesed Pegol|NOX A12|NOXA12 NOX-A12 (olaptesed pegol) binds to CXCL12 and inhibits its interaction with CXCR4 and CXCR7, potentially resulting in increased sensitivity to chemotherapeutic agents, as well as increased infiltration of T-cells into tumors and enhanced anti-tumor immune response in combination with other agents (PMID: 24277076, PMID: 28963140).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References